Cardiovascular T-type calcium channels: physiological and pharmacological significance.
CELLULAR CALCIUM REGULATION: A variety of Ca2+ control processes are responsible for Ca2+ homeostasis and signaling. Voltage-gated Ca2+ channels are dominant in the cardiovascular system. VOLTAGE-GATED Ca2+ CHANNELS: There are several distinct subclasses of Ca2+ channels, distinguished by location, biophysical, structural and pharmacological characteristics. They include both high- and low-voltage-activated channels. The long-lasting (L) type of high-voltage-activated channel is well characterized and is the site of action for the existing clinically available Ca2+ channel antagonists: nifedipine, verapamil and diltiazem. T-TYPE Ca2+ CHANNELS: The low-voltage-activated transient (T-type) channel is widespread in the cardiovascular system and in neurons. It serves pacemaking functions and supports Ca2+ signaling in secretory cells and vascular smooth muscle. The T-type channel also functions in cell growth processes under physiological and pathological conditions. MIBEFRADIL AS A T-TYPE Ca2+ CHANNEL ANTAGONIST: Mibefradil (Ro 40-5967) is a structurally novel Ca2+ antagonist with selectivity for T-type over L-type channels. This selectivity may underlie its vasodilating activity and heart rate depressive effect, its lack of negative inotropy and its cardioprotective properties.
Triggle
D J
DJ
Graduate School, State University of New York, Buffalo 14260-1200, USA.
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002319:Cardiovascular System / Q000378:metabolism*; D006801:Humans; D020748:Mibefradil; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013764:Tetrahydronaphthalenes; D020748:Mibefradil; D002118:Calcium